Exscientia Receives First CTA Approval to Initiate IGNITE-AI, a Phase 1/2 Trial of EXS-21546 in Patients with Advanced Solid Tumours

Exscientia plc (Nasdaq: EXAI) today announced clinical trial application (CTA) approval of IGNITE-AI, enabling site activation in its first European country. IGNITE-AI is a Phase 1/2 trial studying EXS-21546 ('546), Exscientia’s A_2A receptor antagonist in combination with anti-PD-1 therapy in patients with immunotherapy relapsed or refractory renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC). The study will evaluate safety, efficacy, pharmacokinetics and pharmacodynamics in up to 110 patients. Exscientia intends to expand to additional tumour types, including breast cancer, in future trials after assessment of ‘546 activity and validation of its selection biomarkers.

"High adenosine levels in the tumour microenvironment have the potential to suppress immune function, which can inhibit the efficacy of checkpoint inhibitors," said Dr. Michael Krams, Chief Quantitative Medicine Officer of Exscientia. "We have designed this trial not only to learn about ‘546, but also to enhance our confidence in our patient enrichment strategy. We place a strong emphasis on biomarker qualification, because our goal is to identify the right patients for the right treatment."

Exscientia used simulation guided clinical trial design to determine the operating characteristics of the two stages of the trial. The first stage will apply a continuous reassessment model to use accruing data from the dose escalation phase to establish the maximum tolerated dose (MTD) of Exscientia’s A_2A receptor antagonist. Once the MTD is identified with sufficient confidence, the study will advance to the second stage, where the MTD is applied to an expansion cohort. The goal of the expansion phase is to create evidence of efficacy of '546 in combination with a PD-1 inhibitor as well as further enhance confidence in Exscientia's biomarker signature.

At a medical meeting in December, Exscientia will present data on its novel multi-gene signature for identifying high adenosine patient populations, referred to as the adenosine burden score (ABS). IGNITE-AI is designed to prospectively evaluate the ABS in comparison to patient responses in order to validate its use in patient selection. Once statistical confidence in the ABS has been reached, the Company plans to apply the biomarker signature to directly enrich the patient population in clinical development.